Staff Pages

Dr Ron Chen

PhD, Imperial College London University Academic Fellowship in Pervasive TranscriptionSchool of Molecular and Cellular Biology

Background: Studied viral immunoevasion at Imperial College London in the Lab of Prof. Geoffrey Smith FRS. Subsequently worked with Prof. Julie Ahringer FMedSci on functional genomics at the Gurdon Institute, University of Cambridge. Appointed University Academic Fellow 2015.

Studying chromatin regulation in metazoan development to understand disease

We are interested in evolutionarily conserved biological processes in metazoan development. Our current research focuses on how chromatin regulation underlies the trans-differentiation steps, which would shed light on the pathogenesis process for the onset of human diseases including cancer. To address our big biological questions, we use the powerful genetic model organism C. elegans that share 70% of proteins encoded in the human genome. Most proteins involved in transcription and chromatin function are highly conserved. The comprehensive genetic tools (e.g. the genome-wide RNAi library), genomic information (e.g. modENCODE datasets), short life cycle (only 3 days), and the ease of molecular experiments (e.g. CRISPR genome editing) all make C. elegans a great experimental system to address basic biological questions at the organismal level. In parallel, we also use tissue-cultured mammalian cells to "translate" our worm work in order to aid the understanding of the underlying mechanism of human diseases.

CpG-islands: a HOT regulatory platform for epigenetic control

CpG-rich promoters are frequently present across the C. elegans and human genome. Both worm and human CpG-rich coding promoters are highly accessible, marked by H3K4me3, and enriched for widely expressed active genes (Chen et al., 2013 Genome Research & Chen et al., 2014 Genome Research). The finding was highly surprising as CpG island promoters were only thought to have genomic significance in mammals. Currently, C. elegans is the only invertebrate genome showing mammalian CpG-island-like features. This makes C. elegans an attractive model to study conserved transcription regulation events, especially the function of H3K4me3 modifications and other histone modifications found in most active coding gene promoters enriched for CpGs. These widely active genomic regions have been found to harbour highly occupied target (HOT) regions for transcription factors in both C. elegans and humans (Chen et al., 2014 Genome Research). It suggests that CpG-dense promoters can function as regulatory hubs for chromatin regulators and consequently may modulate transcriptional activities.

CFP-1 is an evolutionarily conserved non-methylated CpG binding protein that binds to CpG-rich promoters in C. elegans (Chen et al., 2014 Genome Research), like in the mammalian genome. This conserved epigenetic regulator is part of the COMPASS complex that contains the major transferase for histone 3 lysine 4 tri-methylation (H3K4me3); SET-2 in C. elegans and Setd1A/B in mammals. H3K4me3 is frequently found in active promote regions, thus it has been used as an active promoter mark. The role of H3K4me3 in gene expression is unclear. To address this key question in epigenetic control, we are characterising cfp-1 and set-2 loss-of-function C. elegans mutants for their ability in inducing gene expression, specifying cell fate, and modulating chromatin architectures.